Hormone Therapy for Postpartum Depression

No longer recruiting at 1 trial location

Overseen By Peter J Schmidt, M.D.

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: National Institute of Mental Health (NIMH)

Must be taking: Estradiol, Progesterone, GnRH agonist

Must not be taking: Birth control pills

Disqualifiers: Endometriosis, Liver disease, Breast cancer, Diabetes, Heart disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore whether postpartum depression links to the sudden drop in hormones like estrogen (specifically estradiol) and progesterone after childbirth. Researchers will simulate pregnancy hormone levels in women who previously experienced postpartum depression to observe if hormone changes affect mood. Participants will either stop hormone treatment after eight weeks or continue it for another month to compare mood changes. Women with a history of postpartum depression who have been symptom-free for at least a year and have regular menstrual cycles may be eligible.

As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to important findings on postpartum depression.

Do I have to stop taking my current medications to join the trial?

Yes, participants must be medication-free, including birth control pills, to join the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that estradiol, a hormone treatment, is usually well-tolerated by women with postpartum depression. Studies have found that using estradiol through a skin patch works well for both postpartum and menopausal women, even those with depression. However, some risks exist. Estradiol can affect breast milk production and may increase the chance of certain side effects.

For progesterone, the evidence is less clear. Some studies suggest that treatments using only progestin (a form of progesterone) might not be ideal for women with a history of postpartum depression or mood disorders. However, strong evidence does not indicate that progesterone increases depression in all cases.

This trial is in an early stage, still investigating the safety of these hormone treatments. Early trials suggest the treatment is safe enough for testing in people, but more research is needed to confirm its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using estradiol and progesterone for postpartum depression because these hormones target the root cause of the condition by addressing hormonal imbalances. Unlike traditional antidepressants, which can take weeks to be effective, hormone therapy may offer a quicker response by directly replenishing the hormones that fluctuate after childbirth. This approach could provide a more tailored treatment for women experiencing postpartum depression, potentially reducing symptoms more rapidly and effectively.

What evidence suggests that this trial's treatments could be effective for postpartum depression?

Research suggests that suddenly stopping hormones like estrogen and progesterone might lead to postpartum depression. This trial will compare different hormone therapies for postpartum depression. Participants in one arm will receive estradiol, a type of estrogen. Studies have shown that estradiol can greatly reduce symptoms of postpartum depression. In one study, women with postpartum depression who used estradiol reported their symptoms decreased by more than 50%. Another arm will involve progesterone, but the results for progesterone are less encouraging. Some studies found that synthetic forms of progesterone do not prevent postpartum depression and might even increase the risk. Overall, estradiol seems promising as a treatment for postpartum depression, while the effectiveness of progesterone remains uncertain. ^{1 2 4 6 7}

Who Is on the Research Team?

Peter J Schmidt, M.D.

Principal Investigator

National Institute of Mental Health (NIMH)

Are You a Good Fit for This Trial?

This trial is for women aged 18-50 who have experienced major depression or mood disorders within three months after childbirth, are in good health, and have had a stable menstrual cycle for at least three months. They should not be pregnant or breastfeeding and must have been well for at least one year without any history of severe postpartum mental health issues.

Inclusion Criteria

I am a woman aged 18-50, had postpartum depression but have been well for over a year, not on medication, and have regular menstrual cycles.

I am a woman aged 18-50, with past depression but well for a year, not on medication, and have regular periods.

Group 3: Normal Controls: Controls will meet all criteria specified except they must not have any past or present Axis I diagnosis or evidence of menstrually related mood disorders.

Exclusion Criteria

Patients will not be permitted to enter this protocol if they have important clinical or laboratory abnormalities including any history of the following: endometriosis; undiagnosed enlargement of the ovaries; liver disease; breast cancer; a history of blood clots in the legs or lungs; undiagnosed vaginal bleeding; porphyria; diabetes mellitus; malignant melanoma; gallbladder or pancreatic disease; heart or kidney disease; cerebrovascular disease (stroke); cigarette smoking; a history of suicide attempts or psychotic episodes requiring hospitalization; recurrent migraine headaches; pregnancy (patients will be warned not to become pregnant during the study and will be advised to employ barrier contraceptive methods; pregnancy-related medical conditions such as hyperemesis gravidarum, pretoxemia and toxemia, deep vein thrombosis (DVT) and bleeding diathesis; Any woman with a first degree relative (immediate family) with premenopausal breast cancer or breast cancer presenting in both breasts or any woman who has multiple family members (greater than three relatives) with postmenopausal breast cancer will also be excluded from participating in this protocol; Any woman meeting the Stages of Reproductive Aging Workshop Criteria (STRAW) for the perimenopause will be excluded from participation. Specifically, we will exclude any woman with an elevated plasma FSH level (greater than or equal to 14 IU/L) and with menstrual cycle variability of > 7 days different from their normal cycle length; Subjects who are unable to provide informed consent; NIMH employees and staff and their immediate family members will be excluded from the study per NIMH policy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Hormonal Treatment

Participants receive estradiol and progesterone after pretreatment with a GnRH agonist (Lupron) to establish supraphysiologic plasma levels of gonadal steroids.

8 weeks

Placebo or Continued Hormonal Treatment

One group receives placebo for 4 weeks after 8 weeks of hormonal treatment, while another group continues with hormone addback for an additional 4 weeks.

4 weeks

Follow-up

Participants are monitored for mood, behavioral, and hormonal parameters after treatment.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Estradiol
• Placebo
• Progesterone

Trial Overview The study tests if hormone changes trigger postpartum depression by simulating pregnancy hormones with Estradiol and Progesterone, then suddenly stopping them. Some participants will continue the hormones longer to compare effects on mood and behavior.

How Is the Trial Designed?

Group I: Group 2, Continued Replacement Group Active Control 2 Interventions

12 weeks of hormone addback

Group II: Group 1, Hormone and Placebo Group Placebo Group 3 Interventions

8 weeks of hormonal addback plus 4 weeks of placebo

Estradiol is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Estradiol for:

• Menopausal symptoms
• Hypoestrogenism
• Osteoporosis prevention
• Breast cancer palliation
• Prostate cancer palliation

Approved in United States as Estradiol for:

• Moderate to severe vasomotor symptoms due to menopause
• Vulvar and vaginal atrophy due to menopause
• Hypoestrogenism due to hypogonadism, castration, or primary ovarian failure
• Prevention of postmenopausal osteoporosis
• Palliative treatment of breast cancer
• Palliative treatment of prostate cancer

Approved in Canada as Estradiol for:

• Menopausal symptoms
• Hypoestrogenism
• Osteoporosis prevention
• Breast cancer palliation
• Prostate cancer palliation

Who Is Running the Clinical Trial?

National Institute of Mental Health (NIMH)

Lead Sponsor

Trials

3,007

Recruited

2,852,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2782667/

Transdermal estradiol for postpartum depression: A promising ... Among women with a history of PPD, 63% experienced depressive symptom increase during addition of combined estradiol and progesterone which ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10105981/

Transdermal estradiol for postpartum depression Primary outcome measures were treatment response (> 50% decrease from baseline BDI) and remission (BDI < 10) at 6 weeks, and secondary outcome ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00059228

Clinical Trial of Estrogen for Postpartum Depression This study evaluates the efficacy of estrogen treatment in women with postpartum depression (PPD). PPD causes significant distress to a large number of women.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00744328?term=AREA%5BConditionSearch%5D(%22Postpartum%20Depression%22)%20AND%20AREA%5BInterventionSearch%5D(%22Estradiol%203-benzoate%22)&rank=1

Postpartum Depression : Transdermal Estradiol Versus ... The purpose of this study is to determine whether estrogen patches are effective for the treatment of postpartum major depression, as compared to sertraline ( ...

5. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.950004/full

A systematic review and network meta-analysis Among several active antidepressants, we found that only estradiol was significantly more effective than sertraline. The SUCRA indicated that ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19661765/

Transdermal estradiol for postpartum depression We conclude that estradiol treatment for PPD requires confirmation of efficacy in a randomized clinical trial before routine clinical use as monotherapy.

7. womensmentalhealth.org womensmentalhealth.org/posts/estrogen-posptartum-depression/

Can Estrogen Be Used to Treat Posptartum Depression? Estrogen delivered in the acute postpartum period is not without risk and has been associated with changes in breast milk production, as well as an increased ...